ME00716B - Composés et procée pour l'inhibition de progression mitotique - Google Patents

Info

Publication number

ME00716B

ME00716B MEP-2008-109A MEP10908A ME00716B ME 00716 B ME00716 B ME 00716B ME P10908 A MEP10908 A ME P10908A ME 00716 B ME00716 B ME 00716B

Authority

ME

Montenegro

Prior art keywords

ring

aliphatic

group

optionally substituted

hloro

Prior art date

2003-03-07

Links

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• 150000001875 compounds Chemical class 0.000 title claims description 206
• 102000003989 Aurora kinases Human genes 0.000 title claims description 48
• 108090000433 Aurora kinases Proteins 0.000 title claims description 48
• 230000002401 inhibitory effect Effects 0.000 title claims description 8
• 238000000034 method Methods 0.000 title description 79
• 230000005764 inhibitory process Effects 0.000 title description 14
• 230000008600 mitotic progression Effects 0.000 title description 3
• 125000001931 aliphatic group Chemical group 0.000 claims description 244
• 229910052739 hydrogen Inorganic materials 0.000 claims description 176
• 239000001257 hydrogen Substances 0.000 claims description 176
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 154
• 125000001072 heteroaryl group Chemical group 0.000 claims description 127
• 125000000623 heterocyclic group Chemical group 0.000 claims description 119
• 125000003118 aryl group Chemical group 0.000 claims description 104
• -1 cycloaliphatic Chemical group 0.000 claims description 102
• 125000001475 halogen functional group Chemical group 0.000 claims description 88
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 83
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 82
• 229910052757 nitrogen Inorganic materials 0.000 claims description 74
• 229910052799 carbon Inorganic materials 0.000 claims description 65
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 62
• RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims description 57
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 57
• 125000002947 alkylene group Chemical group 0.000 claims description 53
• 125000001424 substituent group Chemical group 0.000 claims description 53
• 125000004432 carbon atom Chemical group C* 0.000 claims description 40
• 229910052760 oxygen Inorganic materials 0.000 claims description 40
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
• 206010028980 Neoplasm Diseases 0.000 claims description 36
• 125000003107 substituted aryl group Chemical group 0.000 claims description 33
• 125000005842 heteroatom Chemical group 0.000 claims description 30
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
• 229910052717 sulfur Inorganic materials 0.000 claims description 28
• 150000003839 salts Chemical class 0.000 claims description 25
• CUJJWOUYYROEOP-UHFFFAOYSA-N 2-benzazepin-2-amine Chemical compound NN1C=CC=C2C=CC=CC2=C1 CUJJWOUYYROEOP-UHFFFAOYSA-N 0.000 claims description 24
• 238000006467 substitution reaction Methods 0.000 claims description 23
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• 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 17
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• 125000006413 ring segment Chemical group 0.000 claims description 10
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• QXUNLRUYUXSFQE-UHFFFAOYSA-N 1h-1-benzazepin-2-amine Chemical compound N1C(N)=CC=CC2=CC=CC=C21 QXUNLRUYUXSFQE-UHFFFAOYSA-N 0.000 claims description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
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• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 5
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
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• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
• 125000001041 indolyl group Chemical group 0.000 claims description 4
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 4
• 125000005956 isoquinolyl group Chemical group 0.000 claims description 4
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
• 201000002528 pancreatic cancer Diseases 0.000 claims description 4
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
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• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000002541 furyl group Chemical group 0.000 claims description 3
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 3
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• 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 3
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
• 125000001544 thienyl group Chemical group 0.000 claims description 3
• 125000001425 triazolyl group Chemical group 0.000 claims description 3
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 2
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 2
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 2
• 238000004519 manufacturing process Methods 0.000 claims description 2
• 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• 125000004306 triazinyl group Chemical group 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 16
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims 2
• HHFBDROWDBDFBR-UHFFFAOYSA-N 4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=NC=C(CN=C(C=2C3=CC=C(Cl)C=2)C=2C(=CC=CC=2F)F)C3=N1 HHFBDROWDBDFBR-UHFFFAOYSA-N 0.000 claims 1
• 101100516806 Caenorhabditis elegans nog-1 gene Proteins 0.000 claims 1
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims 1
• 208000002495 Uterine Neoplasms Diseases 0.000 claims 1
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